crossing96/oncoscreening huggingface dataset:
Prognostic Significance of Programmed Cell Death-1, Programmed Cell Death-Ligand 1, Programmed Cell Death-Ligand 2, and Fibroblast Growth Factor Receptor 3 mRNA Expression in Bladder Cancer.	INTRODUCTION: This study aimed to evaluate the prognostic significance of programmed cell death (PD)-1/PD-ligand 1 (PD-L1), PD-ligand 2 (PD-L2), and fibroblast growth factor receptor 3 (FGFR3) expression in bladder cancer (BC). METHODS: A retrospective study was conducted on BC patients who underwent transurethral resection between 2005 and 2014. Of the initial 136 patients, 31 were excluded for not meeting the inclusion criteria, leaving 105 cases for the final analysis. The mRNA levels of PD-1/PD-L1/PD-L2 and FGFR3 were assessed using quantitative reverse transcription PCR and NanoString technology. RESULTS: High expression of PD-1 and its ligands (PD-L1/PD-L2) showed a strong correlation with each other and was associated with poor clinical outcomes, including higher tumor stage, grade, and cancer-specific mortality (p < 0.001). Conversely, high FGFR3 expression was associated with improved survival and more favorable clinicopathological features. Interestingly, an inverse relationship was observed between FGFR3 and PD-1 (p = 0.032) and PD-L1 (p = 0.016) expression. High mRNA expression profiles of PD-1, PD-L1, PD-L2, and low FGFR3 expression were associated with worse cancer-specific survival (p < 0.001). Multivariate analysis revealed that advanced stage, low FGFR3 expression, and high PD-L2 expression are independent predictors of poor prognosis in BC patients. CONCLUSION: Our findings suggest that elevated levels of PD-1, PD-L1, and PD-L2, combined with reduced FGFR3 expression, may assist in identifying patients with poor outcomes and highlight their potential as prognostic biomarkers in BC.	bladder
Tracing the Evolution of Sex Hormones and Receptor-Mediated Immune Microenvironmental Differences in Prostate and Bladder Cancers: From Embryonic Development to Disease.	"The bladder and prostate originate from the urogenital sinus. However, bladder cancer (BC) is usually classified as an immune ""hot"" tumor, whereas prostate cancer (PCa) is deemed as an immune ""cold"" tumor according to the tumor microenvironment (TME) and clinical outcomes. To investigate the immune differences between BC and PCa, studies are compared focusing on immune regulation mediated by sex hormones and receptors to identify key genes and pathways responsible for the immune differences. From a developmental perspective, it is shown that PCa and BC activate genes and pathways similar to those in the developmental stage. During prostate development, the differential expression and function of the androgen receptor (AR) across cell types may contribute to its dual role in promoting and inhibiting immunity in different cells. Androgen deprivation therapy affects AR function in different cells within the TME, influencing immune cell infiltration and antitumor function. Additionally, estrogenα and estrogenβ exert contrasting effects in PCa and BC, which may hold the potential for modifying the ""cold"" and ""hot"" tumor phenotypes. Future research should target key genes and pathways involved in bladder development to clarify the immune regulatory similarities and differences between BC and PCa."	bladder
Predicting 90-day risk of urinary tract infections following urostomy in bladder cancer patients using machine learning and explainability.	This research aims to design and validate a machine learning model to predict the probability of urinary tract infections within 90 days post-urostomy in bladder cancer patients. Clinical and follow-up information from 317 patients who had urostomy procedures at the First Affiliated Hospital of Shanxi Medical University (May 2018-May 2024) were analyzed. The dataset were partitioned into training and testing sets, and feature selection was executed via the Least Absolute Shrinkage and Selection Operator regression technique. Seven machine learning algorithms were employed: Logistic Regression, K-Nearest Neighbors, LightGBM, Random Forest, XGBoost, Support Vector Machine, and Multi-Layer Perceptron. Performance metrics for the model were assessed using multiple evaluation indicators, including AUC, accuracy, sensitivity, specificity, Positive Predictive Value, Negative Predictive Value, and F1 score. SHapley Additive exPlanations and Local Interpretable Model-agnostic Explanations algorithms were applied for model interpretability. UTIs occurred in 22.08% of patients within 90 days after urostomy. The predictive model pinpointed eight important clinical features. Among the developed models, the SVM model demonstrated the best overall performance with AUC (0.835), accuracy (0.825), precision (0.583), recall (0.778), and F1 score (0.667). This model, designed to assess UTIs risk after urostomy in bladder cancer patients, has been deployed online for healthcare professionals at: https://zqmodel.shinyapps.io/shinydashboard_model/ .	bladder
Individualizing first-line treatment for advanced urothelial carcinoma: A favorable dilemma for patients and physicians.	"The treatment landscape for patients with advanced urothelial carcinoma (UC) has evolved rapidly in recent years. In current guidelines, combination treatment with enfortumab vedotin plus pembrolizumab is the first-line (1L) standard of care, and other recommended 1L treatment options are platinum-based chemotherapy followed by avelumab as switch-maintenance treatment in patients without progression, or combination treatment with nivolumab, cisplatin, and gemcitabine for cisplatin-eligible patients only. Individual patients differ in terms of their health status, disease characteristics, expected toxicities, and treatment preferences; thus, a ""one-size-fits-all"" approach to treatment is unlikely to be optimal. The availability of several treatment options creates the potential for individualized treatment. In this review, we discuss factors that may be considered when selecting 1L treatment for patients with advanced UC, including efficacy and safety data from phase 3 trials and real-world studies, quality of life, patient priorities for treatment, patient and disease characteristics, treatment sequencing, biomarkers, and treatment access and cost. Patients and physicians should discuss the benefit-risk balance of all available 1L options to enable shared decision-making. Longer follow-up from clinical trials and additional real-world studies are needed to further inform treatment selection."	bladder
Gold nanoparticles/Cu decorated metal-organic frameworks for synergistic photodynamic/ferroptosis cancer therapy.	Photodynamic therapy (PDT) holds promise for cancer treatment by generating reactive oxygen species via photosensitizers (PSs) activated by specific wavelengths of light. However, the poor water solubility of PSs and the tumor microenvironment, characterized by high glutathione (GSH) levels and hypoxia, limit its efficacy against hypoxic tumors. To overcome these challenges, we developed a novel nano-reactor, Zr(Cu)-MOF@Au@DHA, to augment PDT-ferroptosis therapy. By incorporating Cu(2+)into the porphyrin ring of PCN-224 and decorating it with gold nanoparticles, we enhanced the photocatalytic efficiency of the metal-organic framework (MOF). Additionally, dihydroartemisinin (DHA) was loaded onto the nano-reactor to boost the ferroptosis sensitivity of bladder cancer cells. Bothin vitroandin vivostudies confirm that under laser irradiation, Zr(Cu)-MOF@Au@DHA significantly elevates oxidative stress, depletes GSH, and triggers DHA release, sensitizing tumor cells to ferroptosis and enhancing PDT-ferroptosis therapy for bladder cancer. This innovative nano-platform integrates near-infrared light-triggered PDT with chemotherapy to induce ferroptosis, addressing critical limitations in bladder cancer treatment.	bladder
Exploring the impact of chronotype, chrononutrition and lifestyle on bladder cancer.	BACKGROUND: The misalignment of sleep and eating patterns with biological cycles is a significant issue that could have detrimental effects on health and is prevalent among cancer patients. Sleep duration, chronotype, and nutrition may be linked to the presence of urothelial tract cancer. Bladder cancer is the most frequently diagnosed cancer in the urinary system. The study estimated bladder cancer patients' nutrition behavior, sleep preferences, and chronotype. METHODS: 101 patients were enrolled. Based on histopathological examination, they were divided into the cancer group (n = 69) and the non-cancer group (n = 32). Lifestyle was assessed through three questionnaires about sleep, chronotype patterns, and chrononutrition behaviors: social jet lag, eating jet lag, eating window, evening and morning latency. The analysis was also completed by assessing salivary alpha-amylase and immunoglobulin A (IgA). RESULTS: In cancer and non-cancer patients, we did not find differences between the chronotypes (p = 0.0634) or other measured factors. Most of the studied population did not present social or eating jet lag and morning or evening latency. In addition, the total sleep duration in these groups was similar 8.5 (5.0-13.0) vs 9.0 (5.0-11.5) hours per day (p > 0.99). The eating window did not differ between the groups (p = 0.061). Furthermore, the assessment of salivary alpha-amylase 193.9 U/ml (10.2-1173.0) and IgA 129.0 μg/ml (5.1-801.1) (p = 0.43; p = 0.18, respectively) showed no differences. CONCLUSIONS: In this preliminary study, we did not observe a domination of particular types of chronotypes in the cancer and non-cancer groups. Moreover, there were no significant changes in lifestyle and chrononutrition behavior, except weak difference between groups in eating window. However, it provides a robust foundation for further research and clinical applications.	bladder
Pathology-based deep learning features for predicting basal and luminal subtypes in bladder cancer.	BACKGROUND: Bladder cancer (BLCA) exists a profound molecular diversity, with basal and luminal subtypes having different prognostic and therapeutic outcomes. Traditional methods for molecular subtyping are often time-consuming and resource-intensive. This study aims to develop machine learning models using deep learning features from hematoxylin and eosin (H&E)-stained whole-slide images (WSIs) to predict basal and luminal subtypes in BLCA. METHODS: RNA sequencing data and clinical outcomes were downloaded from seven public BLCA databases, including TCGA, GEO datasets, and the IMvigor210C cohort, to assess the prognostic value of BLCA molecular subtypes. WSIs from TCGA were used to construct and validate the machine learning models, while WSIs from Shanghai Tenth People's Hospital (STPH) and The Affiliated Guangdong Second Provincial General Hospital of Jinan University (GD2H) were used as external validations. Deep learning models were trained to obtained tumor patches within WSIs. WSI level deep learning features were extracted from tumor patches based on the RetCCL model. Support vector machine (SVM), random forest (RF), and logistic regression (LR) were developed using these features to classify basal and luminal subtypes. RESULTS: Kaplan-Meier survival and prognostic meta-analyses showed that basal BLCA patients had significantly worse overall survival compared to luminal BLCA patients (hazard ratio = 1.47, 95% confidence interval: 1.25-1.73, P < 0.001). The LR model based on tumor patch features selected by Resnet50 model demonstrated superior performance, achieving an area under the curve (AUC) of 0.88 in the internal validation set, and 0.81 and 0.64 in the external validation sets from STPH and GD2H, respectively. This model outperformed both junior and senior pathologists in the differentiation of basal and luminal subtypes (AUC: 0.85, accuracy: 74%, sensitivity: 66%, specificity: 82%). CONCLUSIONS: This study showed the efficacy of machine learning models in predicting the basal and luminal subtypes of BLCA based on the extraction of deep learning features from tumor patches in H&E-stained WSIs. The performance of the LR model suggests that the integration of AI tools into the diagnostic process could significantly enhance the accuracy of molecular subtyping, thereby potentially informing personalized treatment strategies for BLCA patients.	bladder
The impact of age on BCG treatment response.	INTRODUCTION: Bacillus Calmette-Guerin (BCG) is an immunologic treatment for patients with intermediate and high-risk Nonmuscle Invasive Bladder Cancer (NMIBC). It has been hypothesized that age related immune impairment might lead to decreased efficacy of BCG in older patients. One recent single-institution study found no association between age > 70 and worse oncologic outcomes in a cohort of 632 patients. We sought to validate these findings using a single institution database of NMIBC patients treated with BCG. METHODS: We performed a retrospective analysis of patients diagnosed with NMIBC and treated with adequate BCG between 2000 and 2023 at our institution. Patients were divided into two cohorts based on age at NMIBC diagnosis: age ≤ 70 years and age > 70 years. Fine-Gray competing risk survival analysis was performed to assess for differences in the cumulative incidence of high-grade recurrence (HGR), progression (progression to muscle invasive bladder cancer or distant metastasis) and bladder cancer specific mortality (CSM) according to patient age. RESULTS: We identified 473 patients treated with adequate BCG. 232 patients (49%) were aged ≤ 70 and 241 (51%) were aged > 70. Neither cohort differed significantly in terms of race, sex, or tumor characteristics. On competing risk analysis age > 70 was not significantly associated with increased HGR (HR 0.77; 95% CI 0.59-1.02, P = 0.06), progression (HR 1.17; 95% CI 0.62-2.18, P = 0.63), or CSM (HR 1.12; 95% CI 0.42-2.95, P = 0.82). CONCLUSION: We did not observe an association between age > 70 and increased HG recurrence, bladder cancer progression, or CSM. Our results are consistent with other recent series and suggest that BCG efficacy in NMIBC is not negatively affected by increased patient age.	bladder
Senescence-specific molecular subtypes stratify the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer.	BACKGROUND: Bladder cancer (BLCA) is notably associated with advanced age, characterized by its high incidence and mortality among the elderly. Despite promising advancements in models that amalgamate molecular subtypes with treatment and prognostic outcomes, the considerable heterogeneity in BLCA poses challenges to their universal applicability. Consequently, there is an urgent need to develop a new molecular subtyping system focusing on a critical clinical feature of BLCA: senescence. METHODS: Utilizing unsupervised clustering on the Cancer Genome Atlas Program (TCGA)-BLCA cohort, we crafted a senescence-associated molecular classification and precision quantification system (Senescore). This method underwent systematic validation against established molecular subtypes, treatment strategies, clinical outcomes, the immune tumor microenvironment (TME), relevance to immune checkpoints, and identification of potential therapeutic targets. RESULTS: External validations were conducted using the Xiangya cohort, IMvigor210 cohort, and meta-cohort, with multiplex immunofluorescence confirming the correlation between Senescore, immune infiltration, and cellular senescence. Notably, patients categorized within higher Senescore group were predisposed to the basal subtype, showcased augmented immune infiltration, harbored elevated driver gene mutations, and exhibited increased senescence-associated secretory phenotype (SASP) factors expression in the transcriptome. Despite poorer prognoses, these patients revealed greater responsiveness to immunotherapy and neoadjuvant chemotherapy. CONCLUSIONS: Our molecular subtyping and Senescore, informed by age-related clinical features, accurately depict age-associated biological traits and its clinical application potential in BLCA. Moreover, this personalized assessment framework is poised to identify senolysis targets unique to BLCA, furthering the integration of aging research into therapeutic strategies.	bladder
Outcomes of BCG vs upfront radical cystectomy for high-risk non-muscle-invasive bladder cancer.	OBJECTIVE: To assess the oncological outcomes of patients with high-risk (HR) and very high-risk (VHR) non-muscle-invasive bladder cancer (NMIBC) treated with upfront radical cystectomy (RC) vs Bacillus Calmette-Guérin (BCG) instillations from a contemporary European multicentre cohort. PATIENTS AND METHODS: We conducted a retrospective analysis of 1491 patients diagnosed with HR- or VHR-NMIBC from a European multicentre database between 2015 and 2024. Patients were included if they received either upfront RC or at least five doses of BCG. A 1:1 propensity score matching (PSM) according to clinically relevant variables was applied. Progression was defined as muscle-invasive or metastatic disease. Cumulative incidence plots and multivariable competing risk regression models addressing cancer-specific mortality (CSM) were fitted. RESULTS: Among the 1221 patients with HR- (n = 1221 [90%]) or VHR-NMIBC (n = 121 [10%]), 87 (7.1%) underwent upfront RC. The median follow-up was 2.6 years. After PSM (87 vs 87 patients), the 5-year CSM rate was similar in patients treated with BCG (13%) vs their upfront RC counterparts (16%) (hazard ratio: 1.77, 95% confidence interval [CI] 0.66-4.73; P = 0.3). Of the 1134 patients who initially received BCG, 73 (6.6%) eventually required delayed RC, with 34 (47%) progressing to muscle-invasive bladder cancer before delayed RC. The 3-year CSM rate was comparable in upfront RC (13%) vs delayed RC (11%) among non-progressing patients (P = 0.3). However, patients who progressed before delayed RC had worse 3-year CSM relative to those who did not (13% vs 31%, hazard ratio: 0.32, 95% CI 0.13-0.83; P = 0.018). CONCLUSION: Within a European cohort of patients with HR- and VHR-NMIBC, upfront RC was rarely performed. Patients treated with BCG did not exhibit a CSM disadvantage relative to their upfront RC counterparts. After matching, long-term CSM was similar between BCG therapy and upfront RC. Delayed RC, led to worse outcomes if performed after progression, but matched upfront RC when performed before progression, underscoring importance of timely surgery.	bladder
Impact of upper tract urothelial carcinoma history on patients with non-muscle invasive bladder cancer undergoing intravesical chemotherapy.	This study was designed to evaluate the impact of upper tract urothelial carcinoma (UTUC) history on prognosis in patients with non-muscle-invasive bladder cancer (NMIBC) receiving intravesical chemotherapy. We conducted a single center, retrospective, cohort study of 444 NMIBC patients who received intravesical chemotherapy after transurethral resection of the bladder cancer (TURBT) at Peking University People's Hospital from 2000 to 2015. Patients were divided into UTUC-NMIBC group (with UTUC history) and primary NMIBC group (without UTUC history) by presence of previous UTUC. Demographic, clinical and pathologic factors were analyzed. Kaplan-Meier curves and the log-rank test were used to depict and compare recurrence-free survival (RFS) and progression-free survival (PFS) between the two groups. Multivariable Cox regression models were constructed to determine the variables associated with RFS and PFS. Compared to the primary NMIBC group (n = 410), the UTUC-NMIBC group (n = 34) had an older median age [72.0 (65.0-81.0) vs. 66.0 (58-75) years; P = 0.007], a higher incidence of multiple tumors (52.9% vs. 33.9%; P = 0.026) and a higher recurrence rate (52.9% vs. 30.7%; P = 0.008) and worse RFS (P < 0.001). In multivariate analysis, UTUC history was an independent risk factor for recurrence (hazard ratio = 2.242; P = 0.001), but not for progression. Interestingly, subgroup analysis indicated patients with recent UTUC history (≤ 24 months between UTUC and NMIBC diagnoses) were associated with increased recurrence rates (73.7% vs. 26.7%; P = 0.014). Presence of UTUC history was an independent risk factor for recurrence in patients with NMIBC who received intravesical chemotherapy, especially in those with a shorter interval between UTUC and NMIBC diagnoses.	bladder
Practical use of nadofaragene firadenovec-vncg for pharmacists.	ObjectiveTo provide a practical approach to pharmacists regarding the safe and effective use of nadofaragene firadenovec.Data sourcesClinical study data and pharmacist experience in institutional settings.Data summaryThis review article discusses the role of pharmacists caring for patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) receiving nadofaragene firadenovec. Pharmacist roles in a multidisciplinary care team are described and involve considerations surrounding nadofaragene firadenovec, including its mechanism of action, indication, handling, storage, administration, adverse event profile, disposal, counseling, and other practical points.ConclusionsPharmacists are positioned to be key contributors to the care team regarding the effective use of nadofaragene firadenovec. Further awareness and education will continue to optimize the clinical use of nadofaragene firadenovec in the high-risk BCG-unresponsive NMIBC setting.	bladder
Management and desensitization to Avelumab in anaphylaxis and metastatic urothelial carcinoma: A case report.	IntroductionUrothelial carcinoma is the prevailing type of bladder cancer, characterized by expression of the programed death-ligand-1-protein (PD-L1). Avelumab is an anti-PD-L1 monoclonal antibody used in urothelial carcinoma. It is associated with an incidence of 47.4% and 25.2% in grade 3 adverse events or greater, respectively; gastrointestinal symptoms and cutaneous affections are the most common.Case reportA 52-year-old male with a history of rectal cancer and non-muscle-invasive bladder carcinoma. PET/CT revealed adenopathies in the pelvic region, the biopsy confirmed metastatic urothelial carcinoma. Next PET/CT indicated progression. Treatment with Cisplatin + Gemcitabine led to complete response after 4 cycles. Maintenance with Avelumab was indicated. Fifteen minutes after the first Avelumab administration, the patient experienced hypotension, presyncope, skin itching, and nasal congestion. Epinephrine, hydrocortisone, and physiological solution were administered, with resolution of symptoms.Management & outcomeSince Avelumab is first-line maintenance therapy in this patient, a desensitization protocol was performed with (3-bag, 12-steps). The patient was premedicated with acetaminophen and chlorpheniramine. The protocol was successfully completed without hypersensitivity reactions for 6 cycles.DiscussionPatients with hypersensitivity reactions to their first line of treatment are challenged to continue the best approach. We detail the case of a patient diagnosed with metastatic urothelial carcinoma who underwent a desensitization protocol for Avelumab after presenting a severe allergic reaction. The patient tolerated Avelumab throughout the protocol with no complications, achieving the total dosage for his maintenance therapy; drug desensitization is a safe and effective procedure in patients with hypersensitivity reactions to their first-line treatment.	bladder